Metabolic targeting of low grade tumors

Abstract

The present disclosure describes a method for detecting and treating a low grade malignant tissue in a subject, comprising administering 5-aminolevulinic acid or a pharmaceutically acceptable salt or ester thereof, to the subject and measuring the fluorescence of the tissue.

1 . A method for detecting and treating a low grade malignant tissue in a subject, the method comprising:
 a) administering an effective amount of 5-aminolevulinic acid (5-ALA), or a pharmaceutically acceptable salt or ester thereof, to the subject;   b) measuring the fluorescence of tissue in the subject; and   c) treating the low grade malignant tissue;
 wherein the fluorescence in the low grade malignant tissue is higher than fluorescence in adjacent tissue. 
   
     
     
         2 . The method of  claim 1 , wherein the low grade malignant tissue has been previously classified as a WHO Grade I or Grade II tumor. 
     
     
         3 . The method of  claim 1 , wherein the low grade malignant tissue has become aggressive, progressive, or recurrent. 
     
     
         4 . The method of  claim 1 , wherein the measuring comprises a surgical microscope modified for fluorescence imaging. 
     
     
         5 . The method of  claim 1 , wherein the measuring comprises measuring fluorescence emission at from about 610 nm to about 720 nm. 
     
     
         6 . The method of  claim 1 , wherein the low grade malignant tissue is tissue of the brain, breast, colon, kidney, liver, ovary, pancreas, prostate, rectum, stomach, or uterus. 
     
     
         7 . The method of  claim 1 , wherein the low grade malignant tissue is a glioma. 
     
     
         8 . The method of  claim 7 , wherein the glioma comprises oligodendroglioma, diffuse astrocytoma, optic pathway glioma, pilocytic astrocytoma, subependymal giant cell astrocytoma, or pleomorphic xanthoastrocytoma. 
     
     
         9 . The method of  claim 1 , wherein the treating the low grade malignant tissue comprises sonodynamic therapy. 
     
     
         10 . The method of  claim 1 , wherein the treating the low grade malignant tissue comprises surgery. 
     
     
         11 . The method of  claim 1 , wherein the treating the low grade malignant tissue comprises radiation. 
     
     
         12 . The method of  claim 1 , wherein the 5-aminolevulinic acid is provided to the low grade malignant tissue by oral administration of an oral formulation, or intravenous administration of an intravenous formulation, to the subject. 
     
     
         13 . The method of  claim 1 , wherein the 5-aminolevulinic acid is provided by intravenous administration. 
     
     
         14 . The method of  claim 1 , wherein the subject is human. 
     
     
         15 . The method of  claim 1 , wherein the effective amount of 5-ALA is between about 1 mg/kg body weight and 100 mg/kg body weight. 
     
     
         16 . The method of  claim 1 , wherein the effective amount of 5-ALA is between about 10 mg/kg body weight and 75 mg/kg body weight. 
     
     
         17 . A kit for detecting a low grade malignant tissue in a subject, the kit comprising an effective amount of 5-aminolevulinic acid (5-ALA), or a pharmaceutically acceptable salt or ester thereof, and instructions for use. 
     
     
         18 . A system for detecting a low grade malignant tissue in a subject, the system comprising:
 a) an effective amount of 5-aminolevulinic acid (5-ALA), or a pharmaceutically acceptable salt or ester thereof; and   b) a fluorescence-detecting device.   
     
     
         19 . The system of  claim 18 , wherein the low grade malignant tissue has been previously classified as a WHO Grade I or Grade II tumor. 
     
     
         20 . The system of  claim 18 , wherein the low grade malignant tissue has become aggressive, progressive, or recurrent. 
     
     
         21 . The system of  claim 18 , wherein the fluorescence-detecting device comprises a surgical microscope modified for fluorescence imaging.